The embryonic plan of mammals is inherently feminine. Male development is uner the control of two major regulatory genes; H-Y gene normally residing on the Y, by specifying the plasma membrane protein, controls the testicular development. The X-linked Tfm gene, by specifying the nuclear-cytosol androgen-receptor protein, controls the extragonadal masculine development. The above are relevant to our understanding of sexual differences in the aging process. It appears that relatively late in the life span of males, the H-Y antigen expression in testicular cells and spermatozoa begins a progressive decline. This might be the direct cause of old-age male sterility.